Background: Incretin-based drugs, are commonly prescribed to achieve glycemic goals or prevent cardiorenal events for patients with type 2 diabetes. However, previous studies evaluating the risk for thyroid cancer with incretin-based drugs have reported conflicting findings and have methodological limitations.
Objectives: To investigate the risk of thyroid cancer associated with the use of incretin-based diabetes medications, glucagon-like peptide-1 receptor agonists (GLP1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes.
Methods: By using nationwide healthcare data from Korea from 2013 to 2020, two active comparator new-user cohorts were identified wherein initiators of GLP1RA (first cohort) and DPP-4i (second cohort) were compared with initiators of sodium-glucose cotransporter-2 inhibitors (SGLT-2i). We followed patients from a year after study drug initiation (or cohort entry) until an incident diagnosis of thyroid cancer, switch, death, or end of the study period, whichever occurred first. Outcome was incidence of thyroid cancer, defined as ≥1 diagnosis from an inpatient setting or ≥2 independent diagnoses within 180 days from an outpatient setting using primary and secondary diagnosis position. Stabilized inverse probability treatment weighting methods was applied with Cox models were used to estimate weighted hazard ratios (HR) and 95% confidence interval (CI).
Results: The first cohort included 21,722 new-users of GLP1RA and 326,993 new-users of SGLT-2i, while the second cohort included 904,300 new-users of DPP-4i and 112,017 new-users of SGLT-2i. Over a mean follow-up of 2.4 years, the use of GLP1RA was not associated with an increased risk of thyroid cancer (crude incidence rate GLP1RA 0.57 vs SGLT-2i 0.65 per 1000 person-years; weighted HR 0.98, 95% CI 0.62-1.53). Likewise, during mean follow-up of 2.9 years, the use of DPP-4i was also not associated with an increased risk of thyroid cancer (crude incidence rate: DPP-4i 0.51 vs SGLT-2i 0.58; weighted HR 0.95, 0.79-1.14). Consistent results were found across various sensitivity analyses including MTC, which is a subtype of thyroid cancer (GLP1RA: 0.87, 0.32-2.40; DPP-4i: 1.21, 0.82-1.77), and thyroidectomy, which is an alternative definition to increase validity of thyroid cancer (GLP1RA: 0.94, 0.58-1.53; DPP-4i: 0.95, 0.78-1.14).
Conclusions: In this cohort study, both of incretin-based drugs were not associated with an increased risk of thyroid cancer. Given the advantage of the stable glucose-lowering effect of incretin-based drugs, other than the risk of thyroid cancer should be concerned when assessing the balance of risks and benefits of incretin-based drugs among patients with type 2 diabetes.
